Hemodiafiltration combines both standard hemodialysis and hemofiltration into one process, whereby a dialyzer cartridge containing a high flux membrane is used to remove substances from the blood both by diffusion and by convection. The removal of substances by diffusion is accomplished by establishing a concentration gradient across a semipermeable membrane by flowing a dialysate solution on one side of the membrane while simultaneously flowing blood on the opposite side of the membrane. In existing systems, to enhance removal of substances using hemodiafiltration, a solution called substitution fluid is continuously added to the blood either prior to the dialyzer cartridge (pre-dilution) or after the dialyzer cartridge (post-dilution). An amount of fluid equal to that of the added substitution fluid is ultrafiltered across the dialyzer cartridge membrane carrying with it additional solutes.
Substitution fluid is usually purchased as a sterile/non-pyrogenic fluid (eg. 0.9% saline solution or Ringer's Lactate solution) contained in large flexible bags. The disadvantage of using this type of fluid for hemodiafiltration is the relatively high cost associated with using large volumes during treatment. As a result, methods have been developed for producing substitution fluid on-line by filtration of a non-sterile dialysate through a suitable filter cartridge rendering it sterile and non-pyrogenic. Techniques for online production of substitution fluid have been described in the literature, for example, in B. Canaud, et al., “Hemodiafiltration Using Dialysate as Substitution Fluid”, Artificial Organs, Vol. 12, No. 2 (1987), pp. 188-190. Here, a series of filter cartridges and a substitution pump were used in conjunction with a dialysis machine as a means to generate on-line substitution fluid for the purposes of performing hemodiafiltration. What is not described, however, is how the substitution pump is operated when the blood pump stops or when the dialysis machine goes into bypass which prevents dialysate being delivered to the dialyzer and substitution pump. It is understood by those skilled in the art, that a dialysis machine may suddenly stop the blood pump or go into a dialysate bypass mode in response to a machine alarm condition (eg. due to excessive extracorporeal circuit pressure or a low or high dialysate conductivity reading). When this happens, the substitution pump should immediately be disabled or turned OFF as a means to prevent a hazardous condition from occurring (eg. creating an excessive transmembrane pressure across the dialyzer membrane).
Dialysis machine manufacturers have developed stand-alone dialysis machines with on-line substitution fluid suitable for hemodiafiltration. One example is the Fresenius OnLine Plus™ System, available from Fresenius Medical Care of Bad Homburg, Germany. A second example, available from Gambro AB of Lund Sweden, has been described in the literature, for example, in D. Limido et al., “Clinical Evaluation of AK-100 ULTRA for Predilution HF with On-Line Prepared Bicarbonate Substitution Fluid. Comparison with HD and Acetate Postdilution HF”, International Journal of Artificial Organs, Vol. 20, No. 3 (1997), pp. 153-157. In these systems, control of the substitution fluid pump by the dialysis machine is coordinated in such a manner as to prevent unsafe or hazardous conditions.
In general, dialysis machines are replaced every seven years on average and cost approximately $20,000. Currently there are about 45,000 dialysis machines being used around the world, with only a very small percentage of these machines being capable of performing hemodiafiltration with online substitution fluid. Because hemodiafiltration provides a better treatment over current hemodialysis, there exists a clear need for a clinical practitioner to offer this mode of renal replacement therapy to his/her patients. As an alternative to purchasing a new hemodiafiltration machine (eg. capable of producing online substitution fluid), the present applicants have developed a diafiltration delivery module that enables online hemodiafiltration to be performed safely with an existing ultrafiltration (UF) controlled dialysis machine.